Functional heterogeneity of proto-oncogene tyrosine kinases: the C terminus of the human epidermal growth factor receptor facilitates cell proliferation.

摘要: Previous reports have indicated that the C termini of membrane-associated tyrosine kinases encoded by c-src and c-fms proto-oncogenes a negative effect on their biological activity this is mediated C-terminal residue. To determine whether was true for human epidermal growth factor (EGF) receptor, which also kinase proto-oncogene, we constructed two premature termination mutants, dc19 dc63, delete 19 63 amino acids, respectively, from full-length receptor (hEGFR). The smaller deletion removes residue, while larger most tyrosines; similar deletions are found in v-erbB. As previously shown gene encoding EGF mutants induced EGF-dependent focal transformation anchorage-independent NIH 3T3 cells. However, both dc63 were quantitatively less efficient than with being active dc19. Although displayed lower mutant receptors to be several respects receptor. These parameters included localization, stability absence EGF, half-life presence binding, extent autophosphorylation vitro, phosphorylation an exogenous substrate vitro. Therefore, acids no detectable influence early events. We conclude contrast